NM_000059.4(BRCA2):c.4213A>G (p.Asn1405Asp) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 30, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000587921.3

Allele description [Variation Report for NM_000059.4(BRCA2):c.4213A>G (p.Asn1405Asp)]

NM_000059.4(BRCA2):c.4213A>G (p.Asn1405Asp)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.4213A>G (p.Asn1405Asp)

HGVS:

NC_000013.11:g.32338568A>G
NG_012772.3:g.28089A>G
NM_000059.4:c.4213A>GMANE SELECT
NP_000050.2:p.Asn1405Asp
NP_000050.3:p.Asn1405Asp
LRG_293t1:c.4213A>G
LRG_293:g.28089A>G
LRG_293p1:p.Asn1405Asp
NC_000013.10:g.32912705A>G
NM_000059.3:c.4213A>G

Protein change:

N1405D

Links:

dbSNP: rs1555283633

NCBI 1000 Genomes Browser:

rs1555283633

Molecular consequence:

NM_000059.4:c.4213A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000694751	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 17, 2017)	germline	clinical testing	LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV005327575	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 30, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000694751

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 17, 2017)

germline

clinical testing

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV005327575

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 30, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000694751.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: The BRCA2 c.4213A>G (p.Asn1405Asp) variant involves the alteration of a non-conserved nucleotide and 4/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome. However, these predictions have yet to be functionally assessed. This variant is absent in 119904 control chromosomes (ExAC). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV005327575.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as 4441A>G; Observed in cases and controls in a pancreatic cancer study, but was not observed in any cases in a breast cancer case-control study (Momozawa et al., 2018; Mizukami et al., 2020); This variant is associated with the following publications: (PMID: 31911673, 30287823, 32980694)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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